Comparative study of trastuzumab modification analysis using mono/multi-epitope affinity technology with LC-QTOF-MS

Chengyi Zuo; Jingwei Zhou; Sumin Bian; Qing Zhang; Yutian Lei; Yuan Shen; Zhiwei Chen; Peijun Ye; Leying Shi; Mao Mu; Jia-Huan Qu; Zhengjin Jiang; Qiqin Wang

Journal of Pharmaceutical Analysis (Nov 2024)

Comparative study of trastuzumab modification analysis using mono/multi-epitope affinity technology with LC-QTOF-MS

Chengyi Zuo,
Jingwei Zhou,
Sumin Bian,
Qing Zhang,
Yutian Lei,
Yuan Shen,
Zhiwei Chen,
Peijun Ye,
Leying Shi,
Mao Mu,
Jia-Huan Qu,
Zhengjin Jiang,
Qiqin Wang

Affiliations

Chengyi Zuo: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China
Jingwei Zhou: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China
Sumin Bian: School of Engineering, Westlake University, Hangzhou, 310024, China
Qing Zhang: The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China
Yutian Lei: School of Biomedical Engineering, Sun Yat-sen University, Shenzhen, Guang dong, 518107, China
Yuan Shen: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China
Zhiwei Chen: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China
Peijun Ye: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China
Leying Shi: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China
Mao Mu: Guangdong Institute for Drug Control, Guangzhou, 510663, China
Jia-Huan Qu: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China; Corresponding author.
Zhengjin Jiang: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China; Corresponding author.
Qiqin Wang: Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research of China, Jinan University, Guangzhou, 510632, China; Corresponding author.

Journal volume & issue: Vol. 14, no. 11
p. 101015

Abstract

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Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Published in Journal of Pharmaceutical Analysis

ISSN: 2095-1779 (Print); 2214-0883 (Online)
Publisher: Elsevier
Country of publisher: China
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmaceutical-analysis/

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